FCGRT
Description
The FCGRT (Fc gamma receptor and transporter) is a protein-coding gene located on chromosome 19.
The neonatal fragment crystallizable (Fc) receptor (also FcRn, IgG receptor FcRn large subunit p51, or Brambell receptor) is a protein that in humans is encoded by the FCGRT gene. It is an IgG Fc receptor which is similar in structure to the MHC class I molecule and also associates with beta-2-microglobulin. In rodents, FcRn was originally identified as the receptor that transports maternal immunoglobulin G (IgG) from mother to neonatal offspring via mother's milk, leading to its name as the neonatal Fc receptor. In humans, FcRn is present in the placenta where it transports mother's IgG to the growing fetus. FcRn has also been shown to play a role in regulating IgG and serum albumin turnover. Neonatal Fc receptor expression is up-regulated by the proinflammatory cytokine, TNF, and down-regulated by IFN-γ.
== Interactions of FcRn with IgG and serum albumin == In addition to binding to IgG, FCGRT has been shown to interact with human serum albumin. FcRn-mediated transcytosis of IgG across epithelial cells is possible because FcRn binds IgG at acidic pH (<6.5) but not at neutral or higher pH. The binding site for FcRn on IgG has been mapped using functional and structural studies, and involves in the interaction of relatively well conserved histidine residues on IgG with acidic residues on FcRn.
== FcRn-mediated recycling and transcytosis of IgG and serum albumin == FcRn extends the half-life of IgG and serum albumin by reducing lysosomal degradation of these proteins in endothelial cells and bone-marrow derived cells. The clearance rate of IgG and albumin is abnormally short in mice that lack functional FcRn.
FCGRT is a cell surface receptor that transfers passive humoral immunity from the mother to the newborn. It binds to the Fc region of monomeric immunoglobulin gamma (IgG) and mediates its selective uptake from milk. IgG in the milk is bound at the apical surface of the intestinal epithelium. The resultant FCGRT-IgG complexes are transcytosed across the intestinal epithelium and IgG is released from FCGRT into blood or tissue fluids. Throughout life, FCGRT contributes to effective humoral immunity by recycling IgG and extending its half-life in the circulation. Mechanistically, monomeric IgG binding to FCGRT in acidic endosomes of endothelial and hematopoietic cells recycles IgG to the cell surface where it is released into the circulation. In addition to IgG, FCGRT regulates homeostasis of the other most abundant circulating protein albumin/ALB.
FCGRT is also known as FCRN, FcgammaRn, alpha-chain.
